Zusammenfassung
Der Gebärmutterhalskrebs ist weltweit gesehen die zweithäufigste Krebserkrankung der Frau (WHO 1990). Er entsteht über seine Präkanzerose, die zervikale intraepitheliale Neoplasie (CIN). Diese verläuft über drei Schweregrade, CIN 1 bis CIN 3, bevor sie mit einer Latenz von 10 Jahren und mehr in das invasive Plattenepithelkarzinom übergehen kann [72]. Die Prävalenz der CIN zeigte in Westeuropa und den USA eine ständige Zunahme in den letzten zwei Dekaden und liegt bei ca. 3–5% [2,10,82]. Es sind vorwiegend Frauen im reproduktiven Alter zwischen 25 und 40 Jahren betroffen. Die Krebsvorsorge in der westlichen Welt — mit zytologischen Kontrollen im Stadium CIN 1 und 2 (Pap IIID) und chirurgischer Therapie im Stadium CIN 3 (Pap IVa) — bewirkte einen deutlichen Rückgang der Zervixkarzinommortalität um ca. 40%. Allerdings stagniert diese Zahl in den westlichen Ländern seit einem Jahrzehnt. Die Leistungsfähigkeit der klassischen Vorsorge scheint an ihre Grenzen angelangt zu sein. Neue Screening- und Diagnosestrategien werden derzeit auf ihre Wertigkeit im klinischen Alltag überprüft.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
Literatur
The revised Bethesda System for reporting cervical/vaginal cytologic diagnoses: report of the 1991 Bethesda Workshop. J Reprod Med 37: 383–386, 1992
Baken LA, Koutsky LA, Kuypers J, et al: Genital human papillomavirus infection among male and female sex partners: prevalence and type-specific concordance. Journal of Infectious Diseases 171: 429–32, 1995
Barbosa MS, Schlegel R: The E6 and E7 genes of HP V-18 are sufficient for inducing two-stage in vitro transformation of human keratinocytes. Oncogene 4: 1529–32, 1989
Bedell MA, Jones KH, Grossman SR, Laimins LA: Identification of human papillomavirus type 18 transforming genes in immortalized and primary cells. Journal of Virology 63: 1247–1255, 1989
Bergeron C, Barrasso R, Beaudenon S, et al: Human papillomaviruses associated with cervical intraepithelial neoplasia. Great diversity and distinct distribution in low-and high-grade lesions. Am J Surg Path 16: 641–649, 1992
Bibbo M, Dytch HE, Alenghat E, Bartels PH, Wied GL: DNA ploidy profiles as prognostic indicators in CIN lesions. Am J Clin Pathol 92: 261–265, 1989
Böcking A: DNA cytometry. In Surgical Gynecologic Oncology. (Burghardt E, ed). New York: Thieme, 1993, pp 34–38
Böcking A, Hilgarth M, Auffermann W, et al: DNA-cytometric diagnosis of prospective malignancies in borderline lesions of the uterine cervix. Acta cytol 30: 608–615, 1986
Bollmann R, Böcking A: Prognostische Validität der DNA-Bild-Zytometrie bei Dysplasien in Gebärmutterhalsabstrichen. Verh. Dtsch. Ges. Path. 80: 577, 1996
Bosch FX, Manos MM, Munoz N, et al: Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J. Natl. Cancer Inst. 87: 779–780, 1995
Bosch FX, Munoz N, de Sanjose S, et al: Risk factors for cervical cancer in Colombia and Spain. International Journal of Cancer 52: 750–758, 1992
Bosch FX, Schwarz E, Boukamp P, et al: Suppression in vivo of human papillomavirus type 18 E6-E7 gene expression in non-tumorigenic HeLa fibroblast hybrid cells. Journal of Virology 64: 4743–4754, 1990
Burghardt E: Early Histological Diagnosis of Cervical Cancer. Stuttgart: G. Thieme, 1973
Burghardt E, Ostor AG: Site and origin of squamous cervical cancer: A histomorphologic study. Obstetrics and Gynecology 62: 117–127, 1983
Chee YH, Namkoong SE, Kim DH, Kim SJ, Park JS: Immunologie diagnosis and monitoring of cervical cancers using O translated HPV proteins. Gynecol. Oncol. 57: 226–231, 1995
Chow LT, Hirochika H, Nasseri M, et al: Human papilloma virus gene expression. In Papillomaviruses, Cancer Cells (Steinberg BM, Brandsma JL, Taichman LB, eds). Cold Spring Harbor: Cold Spring Harbor Press, 1987, pp 55–67
Clavel C, Bory J-P, Rihet S, et al: Comparative analysis of human papillomavirus detection by hybrid capture assay and routine cytologic screening to detect high-grade cervical lesions. Int. J. Cancer 75: 525–528, 1998
Coppleson M: The origin and nature of premalignant lesions of the cervix uteri. International Journal of Gynecology and Obstetrics 8: 539, 1970
Cox T, Lorincz AT, Schiffman MH, et al: Human papillomavirus testing by hybrid capture appears to be useful in triaging women with a cytologie diagnosis of atypical squamous cells of undetermined significance. Am J Obstet Gynecol 172: 946–954, 1995
Cullen AP, Reid R, Campion M, Lorincz AT: Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasia. Journal of Virology 65: 606–612, 1991
Cuzick J, Szarewski A, Terry G, et al: Human papillomavirus testing in primary cervical screening. Lancet 345: 1533–1536, 1995
Cuzick J, Terry G, Ho L, Hollingworth T, Anderson M: Type-specific human papillomavirus DNA in abnormal smears as a predictor of high-grade cervical intrapithelial neoplasia. Br J Cancer 69: 167–171, 1994
de Villiers EM, Wagner D, Schneider A, et al: Human papillomavirus infections in women with and without abnormal cervical cytology. Lancet i: 703–706, 1987
Durst M, Croce CM, Gissman L, Schwarz E, Huebbner K: Papillomavirus sequences integrate near cellular oncogenes in some cervical carcinomas. Proceedings of National Academy of Sciences, U.S.A. 84: 1070–1074, 1987
Durst M, Kleinheinz A, Hotz M, Gissman L: The physical state of human papillomavirus type 16 DNA in benign and malignant genital tumors. Journal of General Virology 66: 1515–1522, 1985
Ferenczy A, Franco E, Arseneau J, Wright TC, Richart RM: Diagnostic performance of hybrid capture human papillomavirus deoxyribonucleic assay combined with liquid-based cytologic study. Amer. J. Obstet. Gynecol. 175: 651–656, 1996
Ferenczy A, Richard RM: Female reproductive system. Dynamics of scan and transmission electron microscopy. New York: John Wiley&Sons, 1974
Franquemont DW, Ward BE, Anderson WA, Crum CP: Prediction of „high-risk“ cervical papillomavirus infection by biopsy morphology. Am J Clin Pathol 92: 577–582, 1989
Fujii T, Crum CP, Winkler B, Fu YS, Richart RM: Human papillomavirus infection and cervical intraepithelial neoplasia. Histopathology and DNA content. Obstetrics and Gynecology 63: 99–104, 1984
Gaarenstroom KN, Melkert P, Walboomers JMM, et al: Human papillomavirus DNA and genotypes: prognostic factors for progression of cervical intraepithelial neoplasia. International Journal of Gynecologic Cancer 4: 73–78, 1994
Gay JD, Donaldson LD, Goellner JR: False-negative results in cervical cytologie studies. Acta cytol 29: 1043–1048, 1985
Gopalakrishnan V, Khan SA: E1 protein of human papilloma virus 1 a is sufficient for initiation of viral DNA replication. Proc. Natl. Acad. Sci. USA 91: 9597–9601, 1994
Hawley-Nelson P, Vousden KH, Hubbert NL, Lowy DR, Schiller JT: HPV 16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. EMBO Journal 8: 3905–3910, 1989
Hermsen MAJA, Meijer GA, Baak JPA, Joenje H, Walboomers JJM: Comparative genomic hybridization: a new tool in cancer pathology. Hum Pathol 27: 342–349, 1996
Herrington CS, Evans MF, Charnock FM, Gray W, O’McGee J: HPV testing in patients with low grade cervical cytological abnormalities: A follow up study. J. Clinical Pathol. 49: 493–496, 1996
Heselmeyer K, Macville M, Schröck E, et a: Advanced-stage cervical carcinoma are defined by recurrent pattern of chromosomal aberrations revealing high genomic instability and a consistent gain of chromosome arm 3q. Genes, Chromos. Cancer 19: 233–240, 1997
Heselmeyer K, Schröck E, du Manoir S, et al: Gain of chromosome 3q defines the transition from severe dysplasia to invasive carcinoma of the uterine cervix. Proc. Natl. Acad. Sci. USA 93: 479–484, 1996
Hildesheim A, Schiffman MH, Gravitt PE, et al: Persistence of type-specific human papillomavirus infection among cytologically normal women. J. Infect. Dis. 169: 235–240, 1994
Hillemanns P, Ellerbrock TV, McPhillips S, et al: Prevalence of anal human papillomavirus infection and anal cytologie abnormalities in HIV-seropositive women. AIDS 14: 1641–1649, 1996
Hillemanns P, Kimmig R, Huttemann U, Dannecker C, Thaler CJ: Screening for cervical neoplasia by self-assessment for human papillomavirus DNA. Lancet 354: 1970, 1999
Hillemanns P, Tannous-Khuri L, Koulos JP, Talmage D, Wright TC: Localization of Cellular Retinoid-binding Proteins in Human Cervical Intraepithelial Neoplasia and Invasive Carcinoma. Am J Pathol 141: 973–980, 1992
Hillemanns P, Thaler C, Kimmig R: Epidemiologie und Diagnostik der zervikalen intraepit-helialen Neoplasie — Ist das derzeitige Konzept von Screening und Diagnostik der CIN noch aktuell? Gynäkol Geb Rundschau 37: 179–191, 1997
Ho GYF, Burk RD, Klein S, et a: Persistent genital human papillomavirus infection as a risk factor for persistent cervical dysplasia. J. Natl. Cancer Inst. 87: 1365–1371, 1995
Holzer E, Pickel H: Die Ausdehnung des atypischen Plattenepithels an der Zervix. Arch. Geschwulstf. 45: 79, 1975
IARC: Human Papillomaviruses. Lyon: IARC Publications, 1995
Kanda T, Furuno A, Yoshiike K: Human papillomavirus type 16 open reading frame E7 encodes a transforming gene for rat 3Y1 cells. Journal of Virology 62: 610–613, 1988
Kassenärztliche Bundesvereinigung und Spitzenverbände der Krankenkassen: Gesetzliche Krankheitsfrüherkennungsmaßnahmen, Dokumentation der Untersuchungsergebnisse: Männer und Frauen — Krebs 1989 — 1990., 1992
Kimmig R, Kapsner T, Speisberg H, Untch M, Hepp H: DNA cell-cycle analysis of cervical cancer by flow cytometry using simultaneous cytokeratin labeling for identification of tumour cells. J. Cancer. Res. Clin. Oncol. 121: 107–114, 1995
Kiviat N, Koutsky LA, Paavonen J, et al: Prevalence of genital papillomavirus infection among women attending a college student health clinic or a sexually transmitted disease clinic. Journal of Infectious Diseases 159: 293–302, 1989
Kiviat NB, Critchlow CW, Kurman RJ: Reassessment of the morphological continuum of cervical intraepithelial lesions; does it reflect different stages in the progression to cervical carcinoma? In The Epidemiology of Cervical Cancer and Human Papillomavirus (Munoz N, Bosch F, Shah K, et al, eds). Lyons: I.A.R.C., 1992, pp 59–66
Koss LG: Diagnostic Cytology and Its Histopathologic Basis. New York: J.B. Lippincott Company, 1992
Kottmeier HL: Evolution et traitment des epitheliomas. Revue Francaise de Gynecolgic et d’Obstétrique 56: 821–826, 1961
Koutsky LA, Holmes KK, Critchlow CW, et al: A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection. New England Journal of Medicine 327: 1272–1278, 1992
Kühler-Obbarius C, Milde-Langosch K, Loning R, Stegner H-E: Polymerase chain reactionassisted evaluation of low and high grade squamous intraepithelial lesion cytology and reappraisal of the Bethesda systrem. Acta cytol 38: 681–686, 1994
Lambert PF, Spalholz BA, Howley PM: A transcriptional repressor encoded by BPV-1 shares a common carboxy-terminal domain with the E2 transactivator. 50: 69–78, 1987
Leeuwen AM, Ploem-Zaaijer JJ, Pieters WJLM, Hollema H, Burger MPM: The suitability of DNA cytometry for the prediction of the histological diagnosis in women with abnormal cervical smears. Br. J. Ob. Gyn. 103: 359–365, 1996
Lehn H, Ernst TM, Sauer G: Transcription of episomal papillomavirus DNA in human condylomata acuminata and Buschke-Lowenstein tumors. Journal of General Virology 65: 2003–2010, 1984
Londesborough P, Ho L, Terry G, et al: Int. J. Cancer 69: 364–368, 1996
Lorincz AT, Temple GF, Kurman RJ, Jenson AB, Lancaster WD: Oncogenic association of specific human papillomavirus types with cervical neoplasia. Journal of the National Cancer Institute 79: 671–677, 1987
Luesley D, Blomfield P, Dunn J, et al: Cigarette smoking and histological outcome in women with mildly dyskaryotic cervical smears. Br J Obstet Gynaecol 101: 49–52, 1994
Lungu O, Sun XW, Felix J, et al: Relationship of human papillomavirus type to grade of cervical intraepithelial neoplasia. Journal of American Medical Association 267: 2493–2496, 1992
Manos MM, Ting Y, Wright DK, et al: Use of polymerase chain reaction amplification for the detection of genital human papillomaviruses. Cancer Cells 7: 209–214, 1989
Melkert PW, Hopman E, Pptvan den Brule AJ, et al: Prevalence of HPV in cytolmorphologically normal cervical smears, as determined by the polymerase chain reaction, is age-dependent. Int. J. Cancer 53: 919–23, 1993
Nees M, van Wijngaarden E, Bakos E, Schneider A, Dürst M: Identification of novel molecular markers which correlate with HPV-induced tumor progression. Oncogene 16: 2447–2458, 1998
Nenning H, Horn LC, Kühndel K, Bilek K: False positive cervical smears: a cytometric and histological study. Analyt Cell Pathol 9: 61–68, 1995
Park TJ, Richart RM, Sun X-W, Wright TC: Association between HPV type and clonal status of cervical squamous intraepithelial lesions (SIL). Journal of the National Cancer Institute 88: 355–358, 1996
Pfister H: Molecular biology of genital HPV infections. Berlin, Heidelberg: Springer, 1990
Phelps WC, Yee CL, Munger K, Howley PM: The human papillomavirus type 16 E7 gene encodes transactivation and transforming functions similar to those of adenovirus El A. Cell 58: 539–547, 1988
Reagan JW, Ng ABP, Wentz WB: Concepts of genesis and development in early cervical neoplasia. Obstetrical and Gynecological Survey 24: 860–874, 1969
Reid R, Lorincz AT: Human Papillomavirus Tests. Clin Obstet Gynaecol 9: 65–103, 1995
Remmink AJ, Walboomers JMM, Heimerhorst TJMea: The presence of persistent high-risk HPV genotypes in dysplastic cervical lesions is associated with progressive disease: Natural history up to 36 months. Int. J. Cancer 61: 306–311, 1995
Report TW: Report of the Task Force of the Department of Health and Welfare of Canada. Cervical Cancer Screening Programs. The Walton Report. Canadian Medical Association Journal 127: 581, 1982
Richart RM: Colpomicroscopic studies of the distribution of dysplasia and carcinoma in-situ on the exposed portion of the human uterine cervix. Cancer 18: 950, 1965
Rozendaal L, Walboomers JMM, Van der Linden JC, et al: PCR-based high-risk HPV test in cervical-cancer screening gives objective risk assessment of women with cytomorphologically normal cervical smears. Int. J. Cancer 68: 766–769, 1996
Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM: The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63: 1129–1136, 1990
Schiffman M, Kiviat H, Burk R, et al: Accuracy and Interlaboratory reliability of human papillomavirus DNA testing by hybrid capture. J. Clin. Microbiol. 33: 545–550, 1995
Schneider A, Zahm DM, Kirchmayr R, Schneider VL: Screening for cervical intra-epithelial neoplasia grade 2/3: validity of cytologie study, cervicography and human papillomavirus detection. Amer. J. Obstet. Gynecol. 174: 1534–1541, 1996
Seedorf K, Krammer G, Rowekamp W, Durst M, Suhai S: Human papillomavirus type 16 DNA sequence. 145: 181–185, 1985
Smith JW, Townsend DE, Spark RS: Genetic variants of glucose-6-phosphate dehydrogenase in the study of carcinoma of the cervix. Cancer 28: 529–532, 1971
Smotkin D, Wettstein FO: Transcription of human papillomavirus type 16 early genes in a cervical cancer and a cancer-derived cell line and identification of the E7 protein. 83: 4680–4684, 1986
Snijders PJF, van den Brule AJC, Schrijnemakers HFJ, et al: The use of general primers in the polymerase chain reaction permits the detection of a broad spectrum of HPV genotypes. General Virology 71: 173–81, 1990
Soost H-J, Lange H-J, Lehmacher W, Ruffing-Kullmann B: The validation of cervical cytology — sensitivity, specificity and predictive value. Acta cytol 35: 8–14, 1991
Storey A, Thomas M, Kalita A, et al: Role of a p53 polymorphism in the development of human apilloma-virus associated cancer. Nature 393: 229–233, 1998
Sun X-W, Ferenczy A, Johnson D, et al: Evaluation of the hybrid capture human papillomavirus desoxyribonucleic-acid detection test. Amer. J. Obstet. Gynecol. 173: 1432–1437, 1995
Sun X-W, Kuhn L, Ellerbrock TV, et al: Human papillomavirus infection in women infected with the human immunodeficiency virus. N. Eng. J. Med. 337: 1343–1349, 1997
Syrjänen K, Kataja V, Yliskoski M, Saarikoski S, Chang F: Natural history of cervical human papillomavirus lesions does not substantiate the biologic relevance of the Bethesda system. Obstetrics and Gynecology 79: 675–682, 1992
van den Brule AJC, Class ECJ, du Maine M, et al: Use of anticontamination primers in the polymerase chain reaction for the detection of human papillomavirus genotypes in cervical scrapes and biopsies. Journal of Medical Virology 29: 20–27, 1989
van den Brule AJC, Walboomers JMM, du Maine M, Kenemans P, Meijer CJLM: Difference in prevalence of human papillomavirus genotypes cytomorphologically normal cervical smears is associated with a history of cervical intraepithelial neoplasia. International Journal of Gynecologic Cancer 48: 404–408, 1991
von Knebel Doeberitz M, Rittmüller C, zur Hausen H, Dürst M: Inhibition of tumorigenicity of C4-1 cervical cancer cells in nude mice by HPV 18 E6-E7 antisense RNA. Int. J. Cancer 51: 831–834, 1992
von Knebel-Doeberitz M, Oltersdorf M, Schwarz E, Gissmann L: Correlation of modified human papillomavirus early gene expression with altered growth properties in C4-1 cervical carcinoma cells. Cancer Res. 84: 3780–3786, 1988
Walboomers JM, Jacobs MV, Manos MM, et al: Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189: 12–19, 1999
Walboomers JMM, Meijer CJLM: Do HPV-negative cervical carcinomas exist? J. Pathol. 181: 253–254, 1997
Ward P, Coleman AD, Malcolm DB: Regulatory mechanisms of the papillomaviruses. Trends in Genetics 5: 97–98, 1989
Werness BA, Levine AJ, Howley PM: Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science 248: 76–79, 1990
Willett GD, Kurman RJ, Reid R, et al: Correlation of the histological appearance of intraepit-. helial neoplasia of the cervix with human papillomavirus types. International Journal of Gynecological Pathology 8: 18–25, 1989
Xi LF, Demers GW, Koutsky LA, et al: J. Infect. Dis. 172: 747–755, 1995
Zehbe I, Wilander E: Human papillomavirus infection and invasive cervical neoplasia: a study of prevalence. J. Pathol. 181: 270–275, 1997
zur Hausen H: Human papillomaviruses in the pathogenesis of anogenital cancer. Virology 184: 9–13, 1991
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Hillemanns, P., Kimmig, R., Thaler, C.J. (2001). Einsatz molekularbiologischer Methoden zu Früherkennung und klinischem Management des Zervixkarzinoms. In: Raem, A.M., Braun, R.W., Fenger, H., Michaelis, W., Nikol, S., Winter, S.F. (eds) Gen-Medizin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56818-3_13
Download citation
DOI: https://doi.org/10.1007/978-3-642-56818-3_13
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-63152-8
Online ISBN: 978-3-642-56818-3
eBook Packages: Springer Book Archive